Reactivation of Ancient Viruses May Be Involved in MS Inflammatory Response, Study Says

Reactivation of ancient viruses incorporated into the human genome in the course of evolution may be involved in the acute inflammatory response that is characteristic of multiple sclerosis (MS), a study says.

The findings of the study, “Expression of endogenous retroviruses reflects increased usage of atypical enhancers in T cells,” were published in The EMBO Journal.

Human endogenous retroviruses, or HERVs, are a type of virus derived from ancient viruses that had been incorporated into the human genome during the process of evolution.

HERVs normally are silenced by heterochromatin, a tightly packed region of the DNA sequence in which genes are less accessible. However, in certain autoimmune diseases, including MS, these inhibitory mechanisms fail, and HERVs — termed fossil viruses — are abnormally active.

Although these viruses do not trigger an infection by themselves, they may change the way cells in the body respond to infection and inflammation once they are active.

A team of researchers from the Institut Pasteur in France found that these viral DNA sequences contain specific instructions that, once active, can control the activity of nearby genes involved in the body’s defense.

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They found that HERV sequences were abnormally active in stem cells — undifferentiated cells that are able to give rise to all cell types in the body — but not in differentiated brain cells.

Researchers also found that these viral sequences were abnormally active, although to a lesser extent, in immune T-cells — the killers of the immune system — that had been driven to overactivation after being exposed to a pesticide called dieldrin. This means that stress may lead to the reactivation of HERV sequences in cells that normally would not express them.

Finally, after examining T-cells isolated from MS patients, the team discovered these ancient viral sequences were abnormally active in the vicinity of genes involved in the body’s immune response. This supports the hypothesis that HERVs reactivation may play a role in inflammation associated with MS by triggering the activity of several pro-inflammatory genes.

“Our study shows that reactivation of ancient viruses does not correspond to an infectious phenomenon, but to a defense response of the body when faced with an acute inflammatory phenomenon,” leading to chronic excessive inflammation, Christian Muchardt, PhD, head of the epigenetic regulation unit at the Institut Pasteur, said in a press release.

“The discovery of this mechanism … may one day pave the way for management of MS using small molecules that inhibit chromatin modification enzymes,” Muchardt said.